10 Complex Phenotypes and the Use of Polygenic Scores to Investigate Gene × Environment Interactions for Substance Use

摘要

Genetic phenotypes are typically described as either monogenic (i.e., single allele cause) or complex (i.e., multiple genetic and environmental causes). Monogenic phenotypes follow Mendel's laws of inheritance (autosomal or X-linked, dominant or recessive) and genetic disorders (e.g., cystic fibrosis, fragile X syndrome) are caused by mutations in a single gene. Complex phenotypes do not necessarily follow Mendel's laws as genes may connect with other genes and/or with environmental exposures to predict a given phenotype (e.g., diabetes, substance dependence) or intermediate pheno-type （e.g., impulsivity, stress reactivity). Genes associated with complex phenotypes are often referred to as susceptibility genes and their joint contributions with other genes and environments greatly increase the conceptual, methodological, and computational challenges for investigators. This chapter focuses on complex phenotypes and the presentation and development of some conceptual and analytic issues and methods that may be used to address G × E relationships.